Antimicrobial polymers

Patent metadata

Field	Value
Publication number	US-10172974-B2
Application number	US-201715409955-A
Country	US
Kind code	B2
Filing date	Jan 19, 2017
Priority date	Jan 19, 2016
Publication date	Jan 8, 2019
Grant date	Jan 8, 2019

Abstract

In one aspect, compositions are described herein. In some embodiments, a composition described herein comprises the reaction product of (i) an alkoxylated or alkenoxylated citric acid, citrate, or ester of citric acid, and optionally a non-alkoxylated and non-alkenoxylated citric acid, citrate, or ester of citric acid, with (ii) a polyol. Additionally, in some cases, a composition described herein comprises the reaction product of (i) and (ii) above and (iii) one or more additional monomers. In some cases, the composition is cross-linked by the use of one or more oxidants such as sodium periodate (NaIO4) and/or silver nitrate (AgNO3), which can be reduced into a reduced oxidant that provides short-term antimicrobial activity. Such a composition can have both short-term and long-term antibiotic and antifungal activity.

First claim

The invention claimed is:

1. A composition comprising:
a polymer or oligomer formed from one or more monomers of Formula (A1), one or more monomers of Formula (B1), (B2), or (B3), and optionally, a monomer according to Formula (A2):

wherein X 1 , X 2 , X 3 , X 4 , X 7 , X 8 , and X 9 are each independently —O— or —NH—;
R 1 , R 2 , and R 3 are independently —H, a C1 to C22 alkyl or alkenyl group, or M + ;
R 4 is —C(O)R 5 ;
R 5 is a C4 to C22 alkyl or alkenyl group;
R 23 , R 24 , and R 25 are independently —H, a C1 to C22 alkyl or alkenyl group, or M + ;
R 26 is —H or M + ;
M + is a monovalent metal cation;
R 6 is —H, —NH, —OH, —OCH 3 , —OCH 2 CH 3 , —CH 3 , or —CH 2 CH 3 ;
R 7 is —H, or a C1 to C22 alkyl or alkenyl group;
R 8 is —H, a C3 to C22 alkyl or alkenyl group, —CH 2 CH 2 OH, or —CH 2 CH 2 NH 2 ; and
n and m are independently integers ranging from 1 to 20.

2. The composition of claim 1 , wherein the polymer or oligomer is formed from one or more monomers of Formula (A1), one or more monomers of Formula (B1), (B2), or (B3), and one or more monomers of Formula (C), Formula (D1), Formula (D2), Formula (D3), Formula (D4), Formula (E1), Formula (E2), Formula (F), Formula (G), Formula (H1), Formula (H2), Formula (H3), Formula (I1), Formula (I2), Formula (I3), Formula (I4), Formula (I5), and/or Formula (I6), and optionally one or more monomers of Formula (A2):

wherein R 9 , R 10 , R 11 , and R 12 are each independently —H, —OH, —CH 2 (CH 2 ) x NH 2 , —CH 2 (CHR 13 )NH 2 , —CH 2 (CH 2 ) x OH, —CH 2 (CHR 13 )OH, or —CH 2 (CH 2 ) x COOH;
R 13 is —COOH or —(CH 2 ) y COOH;
x is an integer ranging from 0 to 10;
y is an integer ranging from 1 to 10;
p is an integer ranging from 1 to 10;
R 14 is —OH, —OCH 3 , —OCH 2 CH 3 , or —Cl;
R 15 is an amino acid side chain;
q is an integer ranging from 1 to 20;
X 5 is —O— or —NH—;
R 16 is —CH 3 or —CH 2 CH 3 ;
R 17 and R 18 are each independently —CH 2 N 3 , —CH 3 , or —CH 2 CH 3 ;
X 6 and Y are each independently —O— or —NH—;
R 19 and R 20 are each independently —CH 3 or —CH 2 CH 3 ;
R 21 is —O(CO)C≡CH, —CH 3 , or —CH 2 CH 3 ; and
R 22 is —CH 3 , —OH or —NH 2 .

3. The composition of claim 1 , wherein the polymer or oligomer is formed from one or more monomers of Formula (A1), one or more monomers of Formula (B1), (B2), or (B3), one or more monomers of Formula (C), and optionally one or more monomers of Formula (A2):

wherein R 9 , R 10 , R 11 , and R 12 are independently —H, —CH 2 (CH 2 ) x NH 2 , —CH 2 (CHR 13 )NH 2 , or —CH 2 (CH 2 ) x COOH;
R 13 is —COOH or —(CH 2 ) y COOH;
x is an integer ranging from 0 to 10; and
y is an integer ranging from 1 to 10.

4. The composition of claim 2 , wherein the polymer or oligomer is formed from one or more monomers comprising maleic acid, maleic anhydride, or fumaric acid.

5. The composition of claim 3 , wherein at least one monomer of Formula (C) is dopamine, L-DOPA, D-DOPA or 3,4-dihydroxyhydrocinnamic acid.

6. The composition of claim 1 , wherein the polymer or oligomer is formed from one or more monomers comprising a diamine.

7. The composition of claim 6 , wherein the diamine has the structure of Formula (G):

wherein q is an integer ranging from 1 to 20.

8. The composition of claim 1 , wherein the polymer or oligomer is formed from one or more monomers comprising one or more alkyne moieties or one or more azide moieties.

9. The composition of claim 8 , wherein the one or more monomers comprising one or more azide moieties comprises a monomer of Formula (H1), (H2), or (H3):

wherein X 5 is —O— or —NH—;
R 16 is —CH 3 or —CH 2 CH 3 ; and
R 17 and R 18 are each independently —CH 2 N 3 , —CH 3 , or —CH 2 CH 3 .

10. The composition of claim 8 , wherein the one or more monomers comprising one or more alkyne moieties comprises a monomer of Formula (I1), (I2), (I3), (I4), (I5) or (I6):

wherein X 6 and Y are each independently —O— or —NH—;
R 19 and R 20 are each independently —CH 3 or —CH 2 CH 3 ;
R 21 is —O(CO)C≡CH, —CH 3 , or —CH 2 CH 3 ; and
R 22 is —CH 3 , —OH or —NH 2 .

11. The composition of claim 8 , wherein the one or more monomers comprising one or more alkyne moieties or one or more azide moieties comprises a peptide, polypeptide, nucleic acid, or polysaccharide.

12. The composition of claim 1 , wherein the composition further comprises a drug dispersed in the polymer or oligomer.

13. The composition of claim 3 , wherein the composition further comprises at least one oxidant.

14. The composition of claim 13 , wherein the oxidant is at least one of sodium periodate (NaIO 4 ) or silver nitrate (AgNO 3 ), and wherein the composition further comprises at least one reduced form of the oxidant.

15. The composition of claim 1 , wherein the polymer or oligomer is crosslinked to form a polymer network.

16. The composition of claim 1 , wherein the composition further comprises nanoparticles dispersed in the polymer or oligomer.

17. A method of treating a microbial infection comprising:
disposing a composition of claim 1 in or on a biological environment.

18. The method of claim 17 , wherein the biological environment is a surface of skin of a living patient.

19. The method of claim 17 , wherein the microbial infection comprises both a bacterial infection and a fungal infection, and the method further comprises:
killing at least 10% of bacteria of the bacterial infection; and
killing at least 10% of fungi of the fungal infection.

20. The method of claim 17 , wherein microbial proliferation in the biological environment is reduced by at least 50% compared to a negative control.

Assignees

• Penn State Res Found

Inventors

• Yang Jian
• Guo Jinshan

Classifications

• A61L26/008

  Hydrogels or hydrocolloids · CPC title

• C08G63/6858

  Polycarboxylic acids and polyhydroxy compounds in which at least one of the two components contains aliphatic unsaturation · CPC title

• C08G63/668

  derived from polycarboxylic acids and polyhydroxy compounds · CPC title

• A61L26/0066

  Medicaments; Biocides · CPC title

• A61L2300/404

  Biocides, antimicrobial agents, antiseptic agents · CPC title